scholarly journals Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish

2021 ◽  
Author(s):  
Megan E Madden ◽  
Daumante Suminaite ◽  
Elelbin Ortiz ◽  
Jason J Early ◽  
Sigrid Koudelka ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Action Potential ◽  
Neural Circuit ◽  
Acoustic Stimuli ◽  
Larval Zebrafish ◽  
Axonal Conduction ◽  
Circuit Function ◽  
Cns Myelination ◽  
Conduction Properties

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, due to their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behaviour. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias towards reorientation behaviour instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.

scholarly journals Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish

2021 ◽  
pp. JN-RM-0842-21
Author(s):  
M.E. Madden ◽  
D. Suminaite ◽  
E. Ortiz ◽  
J.E. Early ◽  
S. Koudelka ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Larval Zebrafish ◽  
Axonal Conduction

scholarly journals Individual neuronal subtypes control initial myelin sheath growth and stabilization

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Heather N. Nelson ◽  
Anthony J. Treichel ◽  
Erin N. Eggum ◽  
Madeline R. Martell ◽  
Amanda J. Kaiser ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Myelin Sheath ◽  
Time Lapse ◽  
Marked Individual ◽  
Larval Zebrafish ◽  
Sheath Formation ◽  
Time Lapse Imaging

Abstract Background In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors. Methods To address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes. Results In the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons. Conclusion We conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

scholarly journals Neural architecture: from cells to circuits

2018 ◽  
Vol 120 (2) ◽  
pp. 854-866 ◽  
Author(s):  
Sarah E. V. Richards ◽  
Stephen D. Van Hooser
Keyword(s):  
Nervous System ◽  
Cerebral Cortex ◽  
Structure Function ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neuronal Morphology ◽  
Neural Architecture ◽  
Synaptic Interactions ◽  
Branching Patterns ◽  
Circuit Function

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.

scholarly journals Loss of PRMT5 promotes PDGFRα degradation during oligodendrocyte differentiation and myelination

2018 ◽  
Author(s):  
Sara Calabretta ◽  
Gillian Vogel ◽  
Zhenbao Yu ◽  
Karine Choquet ◽  
Lama Darbelli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Arginine Methylation ◽  
Platelet Derived Growth Factor ◽  
Oligodendrocyte Differentiation ◽  
The Central Nervous System ◽  
Cns Myelination

SummaryPlatelet derived growth factor receptor α (PDGFRα) signaling is required for proliferation, commitment and maintenance of oligodendrocyte (OL) precursor cells (OPCs). PDGFRα signaling promotes OPC homeostasis and its attenuation signals OPC differentiation and maturation triggering the onset of myelination of the central nervous system (CNS). The initial steps of how PDGFRα signaling is attenuated are still poorly understood. Herein we show that decreased Protein Arginine MethylTransferase5 (PRMT5) expression, as occurs during OPC differentiation, is involved in the down-regulation of PDGFRα by modulating its cell surface bioavailability leading to its degradation in a Cbldependent manner. Mechanistically, loss of arginine methylation at R554 of the PDGFRα intracellular domain reveals a masked Cbl binding site at Y555. Physiologically, depletion of PRMT5 in OPCs results in severe CNS myelination defects. We propose that decreased PRMT5 activity initiates PDGFRα degradation to promote OL differentiation. More broadly, inhibition of PRMT5 may be used therapeutically to manipulate PDGFRα bioavailability.

scholarly journals Microglia-Induced Maladaptive Plasticity Can Be Modulated by NeuropeptidesIn Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Stefano Morara ◽  
Anna Maria Colangelo ◽  
Luciano Provini
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Circuit ◽  
Critical Role ◽  
Adult Life ◽  
Experimental Models ◽  
Brain Diseases ◽  
Maladaptive Plasticity ◽  
The Central Nervous System

Microglia-induced maladaptive plasticity is being recognized as a major cause of deleterious self-sustaining pathological processes that occur in neurodegenerative and neuroinflammatory diseases. Microglia, the primary homeostatic guardian of the central nervous system, exert critical functions both during development, in neural circuit reshaping, and during adult life, in the brain physiological and pathological surveillance. This delicate critical role can be disrupted by neural, but also peripheral, noxious stimuli that can prime microglia to become overreactive to a second noxious stimulus or worsen underlying pathological processes. Among regulators of microglia, neuropeptides can play a major role. Their receptors are widely expressed in microglial cells and neuropeptide challenge can potently influence microglial activityin vitro. More relevantly, this regulator activity has been assessed alsoin vivo, in experimental models of brain diseases. Neuropeptide action in the central nervous system has been associated with beneficial effects in neurodegenerative and neuroinflammatory pathological experimental models. This review describes some of the mechanisms of the microglia maladaptive plasticityin vivoand how neuropeptide activity can represent a useful therapeutical target in a variety of human brain pathologies.

Sensory neurons in leech central nervous system: changes in potassium conductance an excitation threshold

1976 ◽  
Vol 39 (6) ◽  
pp. 1184-1192 ◽  
Author(s):  
W. R. Schlue
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Membrane Potential ◽  
Action Potential ◽  
Sensory Neurons ◽  
Potassium Concentration ◽  
Potassium Conductance ◽  
Extracellular Potassium ◽  
Extracellular Potassium Concentration ◽  
Accommodation Coefficients

1. The sensory neurons in the leech central nervous system differ in their accommodation to linearly rising currents. Advantage was taken of these differences to study the ionic mechanism of accommodation in single pairs of N (noxious), P (pressure), and T (touch) cells. 2. Nonlinearities in membrane-potential changes and current-voltage relationships with square-wave and ramp currents are more pronounced in P and T cells than in N cells. The accommodation coefficients increase in conditions that reflect this delayed rectification. When rectification is absent, the accommodation coefficients depart from unity only slightly or not at all. 3. Accommodation coefficients remain unchanged when half of the chloride in the bathing medium is replaced by sulfate. Accommodation coefficients become greater when the extracellular potassium concentration is reduced from 4 to 0 mM, and decrease when the concentration is raised to 8 mM. The membrane potential changes by only a few millivolts. 4. As extracellular potassium concentration is increased, the action potential is lengthened and the maximal rate of fall of the action potential is reduced. With concentrations greater than 4 mM these relationships are linear, but depart from linearity at lower concentrations. The amplitude of the undershoot decreases linearly as the extracellular potassium concentration increases from 4 to 16 mM, and increases non-linearly at concentrations below 4 mM. 5. The rapid accommodation of leech neurons is based primarily on an increased potassium conductance. The possibility is considered that concentration changes like those produced experimentally may occur naturally, affecting integrative processes in the central nervous system.

scholarly journals Fbxw7 is a critical regulator of Schwann cell myelinating potential

2018 ◽  
Author(s):  
Breanne L. Harty ◽  
Fernanda Coelho ◽  
Sarah D. Ackerman ◽  
Amy L. Herbert ◽  
David A. Lyons ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Myelin Sheaths ◽  
Unmyelinated Axons ◽  
Single Axon ◽  
The Central Nervous System ◽  
Mutant Phenotypes ◽  
Cns Myelination

SUMMARYMyelin insulates and protects axons in vertebrate nervous systems. In the central nervous system (CNS), oligodendrocytes (OLs) make numerous myelin sheaths on multiple axons, whereas in the peripheral nervous system (PNS) myelinating Schwann cells (SCs) make just one myelin sheath on a single axon. Why the myelinating potentials of OLs and SCs are so fundamentally different is unclear. Here, we find that loss of Fbxw7, an E3 ubiquitin ligase component, enhances the myelinating potential of SCs. Fbxw7 mutant SCs are seen myelinating multiple axons in a fashion reminiscent of OLs as well as aberrantly myelinating large axons while simultaneously ensheathing small unmyelinated axons - typically distinct roles of myelinating SCs and non-myelinating Remak SCs, respectively. We found that several of the Fbxw7 mutant phenotypes, including the ability to generate thicker myelin sheaths, were due to dysregulation of mTOR. However, the remarkable ability of mutant SCs to either myelinate multiple axons or myelinate some axons while simultaneously encompassing other unmyelinated axons is independent of mTOR signaling. This indicates distinct roles for Fbxw7 in regulating multiple aspects of SC behavior and that novel Fbxw7-regulated mechanisms control modes of myelination previously thought to fundamentally distinguish myelinating SCs from non-myelinating SCs and OLs. Our data reveal unexpected plasticity in the myelinating potential of SCs, which may have important implications for our understanding of both PNS and CNS myelination and myelin repair.

Myelin Plasticity and Nervous System Function

2018 ◽  
Vol 41 (1) ◽  
pp. 61-76 ◽  
Author(s):  
Michelle Monje
Keyword(s):  
Nervous System ◽  
Neural Circuit ◽  
Neurological Function ◽  
Nervous System Activity ◽  
Second Mode ◽  
Nervous System Function ◽  
Plastic Changes ◽  
Circuit Function ◽  
Activity Dependent ◽  
Development Proceeds

Structural plasticity in the myelinated infrastructure of the nervous system has come to light. Although an innate program of myelin development proceeds independent of nervous system activity, a second mode of myelination exists in which activity-dependent, plastic changes in myelin-forming cells influence myelin structure and neurological function. These complementary and possibly temporally overlapping activity-independent and activity-dependent modes of myelination crystallize in a model of experience-modulated myelin development and plasticity with broad implications for neurological function. In this article, I consider the contributions of myelin to neural circuit function, the dynamic influences of experience on myelin microstructure, and the role that plasticity of myelin may play in cognition.

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